US5512557A - Coronary heart disease treated with 17βoestradiol - Google Patents
Coronary heart disease treated with 17βoestradiol Download PDFInfo
- Publication number
- US5512557A US5512557A US08/132,369 US13236993A US5512557A US 5512557 A US5512557 A US 5512557A US 13236993 A US13236993 A US 13236993A US 5512557 A US5512557 A US 5512557A
- Authority
- US
- United States
- Prior art keywords
- oestradiol
- patients
- heart disease
- coronary heart
- exercise
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
Definitions
- the present invention relates to the treatment of coronary heart disease and provides a pharmaceutical composition for such treatment, as well as a method for the treatment of coronary heart disease.
- Coronary heart disease arises from damage to the cardiac muscle, the myocardium, caused by insufficient flow of blood in the coronary arteries.
- the reduced flow of blood is termed myocardial ischemia, and the resulting heart damage is reflected in severe attacks of pain known as angina pectoris.
- the attacks of pain may be relieved or prevented using drugs, for example by sublingual administration of nitroglycerin or by the oral use of ⁇ -blocking agents and calcium antagonists.
- coronary heart disease may be treated by a combination of further methods, including the use of other drugs and the use of surgery.
- Coronary heart disease is particularly prevalent in women who have past the time of menopause. Furthermore, an increase in the incidence of heart conditions, including coronary artery disease, angina pectoris and vasomotor disturbance, is associated with the menopause.
- compositions and methods for the therapeutic treatment of coronary heart disease are based on the discovery that an oestrogen improves exercise-induced myocardial ischaemia in female patients with coronary artery disease.
- the present invention provides a pharmaceutical composition for treatment of coronary heart disease, comprising a synthetic or natural oestrogen together with a pharmaceutically acceptable carrier.
- a method for the treatment of coronary heart disease comprises administration of an effective amount of an oestrogen.
- the treatment will generally be chronic but acute treatment is possible.
- the compositions can readily be formulated and administered to suit the mode of treatment.
- the currently preferred oestrogen is 17 ⁇ -oestradiol.
- Another product which may be employed is one prepared from the urine of pregnant mares, such as that sold by Wyeth under the Trade Name "Premarin" and which comprises a number of oestrogens, not all identified.
- the method of treatment of the present invention comprises the steps of:
- administering to said patient an effective amount of an oestrogen.
- the patient can then be monitored for improvement in the heart condition.
- a male of, say, 40 to 60 years or a female of, say, 60 to 75 years will exhibit one or more of the symptoms of coronary heart disease, including exceptional chest pain and shortness of breath.
- the oestrogen can be administered in various forms, depending upon the patient and the desired route of administration which may be oral, parenteral or transdermal.
- suitable formulations for oral administration include tablets, capsules, granules, powders or syrups; and suitable formulations for parenteral administration include injections (which may be intravenous, intramuscular or subcutaneous), drops or suppositories.
- oestrogen is mixed with additives such as those commonly employed in the field of pharmaceutical preparations, including vehicles, binders, disintegrators, lubricants, corrigents, solubilizers, suspending agents and coating agents.
- additives such as those commonly employed in the field of pharmaceutical preparations, including vehicles, binders, disintegrators, lubricants, corrigents, solubilizers, suspending agents and coating agents.
- the active ingredient may be formulated as a skin patch for transdermal application, e.g. the product Estradern manufactured by Ciba Laboratories.
- the dosage may be varied depending on the symptoms, age and body weight of the patient, the route of administration and the form of the preparation.
- the oestrogen may be administered in conjunction with added progesterone from 14-28 days.
- the present invention also provides for the use of an oestrogen in the manufacture of a medicament for the treatment of coronary heart disease, and particularly of coronary heart disease and myocardial ischaemia in female patients, particularly menopausal and post-menopausal women.
- Oestrogens have previously been administered for several medical indications, notably in hormone replacement therapy for menopausal and postmenopausal women.
- the administration of oestrogens is contra-indicated for patients with coronary heart disease, and the pharmacopoeia contain warnings for oestrogen products that they are not to be given to patients with cardiac disease.
- no medical practitioner will prescribe oestrogen for a patient with coronary heart disease.
- Ovarian hormones and in particular 17 ⁇ -oestradiol, are vasoactive substances. They have been shown to increase cardiac output and arterial flow velocity, and decrease vascular resistance, systolic and diastolic blood pressure (see, for example, Am. Heart J. 1987; 114: 1467-1503; N. Engl. J. Med. 1987; 316; 1105-1110; and .Circulation 1987; 75:1102-1109).
- the present invention is exemplified but not limited by the following Examples.
- the study population consisted of 11 female patients with coronary artery disease referred for cardiac evaluation during a 3 month period at the Royal Brompton National Heart & Lung Hospital, London. Patients were included in the study if they had a reproducible positive exercise test ( ⁇ 1 mm of ST segment depression), proven coronary artery disease ( ⁇ 70% diameter stenosis of one or more coronary arteries) and clinical indication of oestrogen deficiency. All but 2 of the women had 17 ⁇ -oestradiol plasma concentrations lower than 200 pmol/l (normal postmenopausal plasma concentration ⁇ 200 pmol/1 ).
- a complete 12-lead electrocardiogram was obtained at rest, every minute during the test, at the end of each stage, at the onset of 1 mm of planar ST segment depression, at peak exercise and every minute during recovery.
- Leads V 2 , V 5 and II were continuously monitored.
- Systolic and diastolic blood pressure were measured at rest and monitored every minute during exercise and recovery.
- a positive response in the electrocardiogram was defined as a horizontal or downsloping ST segment depression ⁇ 1 mm at 60 ms after the J point occurring at least in six consecutive complexes.
- the exercise test was concluded at the point of physical exhaustion, ST segment depression ⁇ 3 min, severe angina, severe dyspnoea or a decline in systolic blood pressure greater than 20 mm Hg.
- Total exercise time, time to myocardial ischaemia, heart rate, blood pressure at the onset of 1 min ST segment depression, maximal ST segment depression and the development of angina during exercise were recorded.
- a blood sample for the evaluation of plasma levels of 17 ⁇ -oestradiol was taken after each test and analyzed using a standard radioimmunoassay method.
- the ST segment 60 ms after the J point, was evaluated after signal averaging using a computer assisted system (CASE Marquette 12) in all 12 leads.
- the lead showing the greatest ST segment depression in the placebo exercise test was selected for analysis. Exercise tests were reviewed in random order by independent, experienced investigators blinded to the clinical data.
- 17 ⁇ -oestradiol plasma concentrations increased from 155 ⁇ 168 to 2531 ⁇ 1192 pmol/l after administration of sublingual 17 ⁇ -oestradiol (normal premenopausal physiological ranges; luteal 368 to 1100 pmol/l, midcycle 785 to 1840 pmol/l, follicular 74 to 368 pmol/1 ). No patients reported any adverse symptoms after administration of either 17 ⁇ -oestradiol or placebo.
- Heart rate and blood pressure were lower at rest after 17 ⁇ -oestradiol (p ⁇ 0.08). There were no differences in the haemodynamic variables either at the time of 1 mm ST segment depression or at peak exercise apart from the heart rate at 1 mm ST segment depression which was higher after 17 ⁇ -oestradiol (p ⁇ 0.02).
- results are similar to those obtained using acutely administered nitroglycerin or nitrates in patients with coronary artery diseases, and may explain some of the protection against coronary artery disease apparent in females before the menopause, and the protective effects of oestrogen replacement therapy in menopausal women.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
__________________________________________________________________________ Difference Placebo 17-β Oestradiol (n = 11) (n = 11) (n = 11) (95% Confidence mean (SD) mean (SD) p Intervals) __________________________________________________________________________ Resting Heart Rate beats/min! 75 (13) 80 (12) 0.08 -5 (-10 to 0.2) Blood Pressure mm Hg! 141 (23) 132 (22) 0.06 9 (-04 to 20) Rate Pressure Product 10681 (2810) 10675 (3109) 0.1 7 (-1163 to 1745) mm Hg x (beats/min)! 1 mm ST Depression Heart Rate beats/min! 117 (18) 124 (20)* 0.02 -10 (-15 to -5)* Blood Pressure mm Hg! 164 (19) 161 (20)* 0.09 -10 (-18 to 23)* Rate Pressure Product 19360 (4243) 19897 (4410)* 0.07 -1600 (-3483 to 59)* mm Hg x (beats/min)! Time seconds! 456 (214) 550 (166)* 0.02 -101 (-154 to -39)* Peak Exercise Heart Rate beats/min) 140 (34) 139 (19) 0.5 1 (-13 to 11) Blood Pressure mm Hg! 165 (31) 171 (20) 0.7 -6 (-21 to 30) Rate Pressure Product 22079 (5994) 24010 (4662) 0.3 -1930 (-4265 to 2224 mm Hg x (beats/min)! Time seconds! 569 (249) 658 (193) 0.01 -89 (-154 to -9) Max ST Depression mm! 1.6 (0.4) 1.2 (0.05) 0.07 -0.4 (0 to 0.7) __________________________________________________________________________ n = 7
Claims (3)
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/132,369 US5512557A (en) | 1993-10-07 | 1993-10-07 | Coronary heart disease treated with 17βoestradiol |
US09/069,397 USRE36701E (en) | 1993-07-15 | 1998-04-29 | Coronary heart disease treated with oestradiol |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/132,369 US5512557A (en) | 1993-10-07 | 1993-10-07 | Coronary heart disease treated with 17βoestradiol |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/069,397 Reissue USRE36701E (en) | 1993-07-15 | 1998-04-29 | Coronary heart disease treated with oestradiol |
Publications (1)
Publication Number | Publication Date |
---|---|
US5512557A true US5512557A (en) | 1996-04-30 |
Family
ID=22453699
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US08/132,369 Ceased US5512557A (en) | 1993-07-15 | 1993-10-07 | Coronary heart disease treated with 17βoestradiol |
US09/069,397 Expired - Fee Related USRE36701E (en) | 1993-07-15 | 1998-04-29 | Coronary heart disease treated with oestradiol |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/069,397 Expired - Fee Related USRE36701E (en) | 1993-07-15 | 1998-04-29 | Coronary heart disease treated with oestradiol |
Country Status (1)
Country | Link |
---|---|
US (2) | US5512557A (en) |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998022113A1 (en) * | 1996-11-15 | 1998-05-28 | University Of Florida Research Foundation, Incorporated | Methods of prevention and treatment of ischemic damage |
US5968918A (en) * | 1997-10-17 | 1999-10-19 | Kanda; Iwao | Method for the prevention of coronary artery spasm |
US6319914B1 (en) | 1993-11-05 | 2001-11-20 | Apollo Biopharmaceuticals, Inc. | Cytoprotective effect of polycyclic phenolic compounds |
US6326365B1 (en) | 1999-07-20 | 2001-12-04 | Apollo Biopharmaceutics, Inc. | Methods of prevention and treatment of ischemic damage |
US6339078B1 (en) | 1999-07-20 | 2002-01-15 | University Of Florida Research Foundation, Inc. | Methods of prevention and treatment of ischemic damage |
US20030069217A1 (en) * | 1993-11-05 | 2003-04-10 | Simpkins James W. | Methods of prevention and treatment of ischemic damage |
US20040127473A1 (en) * | 1996-12-05 | 2004-07-01 | Reed Michael John | Compound |
US20040214769A1 (en) * | 2001-01-05 | 2004-10-28 | Claes Ohlsson | Estrogen receptors |
US20040229856A1 (en) * | 1999-09-21 | 2004-11-18 | Baskaran Chandrasekar | Local delivery of 17-beta estradiol for preventing vascular intimal hyperplasia and for improving vascular endothelium function after vascular injury |
US20050267086A1 (en) * | 2004-05-27 | 2005-12-01 | Migenix Corp. | Compounds and methods for cytoprotection |
US20070141109A1 (en) * | 1999-09-21 | 2007-06-21 | Baskaran Chadrasekar | Local Deliver of 17-Beta Estradiol for Preventing Vascular Intimal Hyperplasia and for Improving Vascular Endothelium Function after Vascular Injury |
US20090075888A1 (en) * | 2007-09-13 | 2009-03-19 | University Of North Texas Health Science Center At Fort Worth | Cardiovascular and Brain Cell Therapy Using Intracellular Ryanodine Receptor Modulation by the Estrogen Receptor Beta |
US20110158947A1 (en) * | 2008-07-11 | 2011-06-30 | Aleksandar Jovanovic | Sulfonylurea receptor and means for treating ischaemia |
-
1993
- 1993-10-07 US US08/132,369 patent/US5512557A/en not_active Ceased
-
1998
- 1998-04-29 US US09/069,397 patent/USRE36701E/en not_active Expired - Fee Related
Non-Patent Citations (39)
Title |
---|
American Heart Association, "Supplement to Circulation vol. 86, No. 4 Oct. 1992, p. I-537, abst 2137, Abstracts from the 65th Scientific Session," (Nov. 16-19, 1992). |
American Heart Association, Supplement to Circulation vol. 86, No. 4 Oct. 1992, p. I 537, abst 2137, Abstracts from the 65th Scientific Session, (Nov. 16 19, 1992). * |
Bain, Christopher, et al., "Use of Postmenopausal Hormones and Risk of Myocardial Infarction," Circulation, vol. 64, No. 1, pp. 42-(1981). |
Bain, Christopher, et al., Use of Postmenopausal Hormones and Risk of Myocardial Infarction, Circulation, vol. 64, No. 1, pp. 42 (1981). * |
Barr, David P. et al. Influences of Estrogen on Lipoproteins in Atherosclerosis Trans. Assoc. Am. Physicians, 1952, 65:102. * |
Bush, Trudy L., et al., "Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the Lipid Research Clinics Program Follow-up Study," Circulation, vol. 75, pp. 1102-1109 (1987). |
Bush, Trudy L., et al., Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the Lipid Research Clinics Program Follow up Study, Circulation, vol. 75, pp. 1102 1109 (1987). * |
Colditz, Graham A. et al., "Menopause and the Risk of Coronary Heart Disease in Women," The New England Journal of Medicine, vol. 316, No. 18, pp. 1105-1110 (1987). |
Colditz, Graham A. et al., Menopause and the Risk of Coronary Heart Disease in Women, The New England Journal of Medicine, vol. 316, No. 18, pp. 1105 1110 (1987). * |
Colditz, Graham A., et al., "Menopause and the Risk of Coronary Heart Disease in Women," The New England Journal of Medicine, vol. 316, No. 8, pp. 1105-1110 (1987). |
Colditz, Graham A., et al., Menopause and the Risk of Coronary Heart Disease in Women, The New England Journal of Medicine, vol. 316, No. 8, pp. 1105 1110 (1987). * |
Earl R. Plunkett, et al; Amer. J. Obstet Gynecol. Jan., 1992, pp. 117 121. * |
Earl R. Plunkett, et al; Amer. J. Obstet Gynecol. Jan., 1992, pp. 117-121. |
Godsland, I. F., et al., "Sex, plasma lipoproteins, and atherosclerosis: Prevailing assumptions and outstanding questions," American Heart Journal: vol. 114, No. 6, pp. 1467-1503 (Dec. 1987). |
Godsland, I. F., et al., Sex, plasma lipoproteins, and atherosclerosis: Prevailing assumptions and outstanding questions, American Heart Journal: vol. 114, No. 6, pp. 1467 1503 (Dec. 1987). * |
Gordon, Tavia, et al., "Menopause and Coronary Heart Disease," Annals of Internal Medicine, vol. 89, No. 2, pp. 167-161 (1978). |
Gordon, Tavia, et al., Menopause and Coronary Heart Disease, Annals of Internal Medicine, vol. 89, No. 2, pp. 167 161 (1978). * |
Hammond, Charles B., "Effects of long-term estrogen replacement therapy," Am J. Obstet Gynecology, vol. 133, No. 5, pp. 525-536 (1979). |
Hammond, Charles B., Effects of long term estrogen replacement therapy, Am J. Obstet Gynecology, vol. 133, No. 5, pp. 525 536 (1979). * |
Petitti, Diana B., et al. "Risk of Vascular Disease in Women," JAMA, vol. 242, No. 11, pp. 1150-1154 (1979). |
Petitti, Diana B., et al. Risk of Vascular Disease in Women, JAMA, vol. 242, No. 11, pp. 1150 1154 (1979). * |
Pfeffer, R. I., et al., "Coronary Risk and Estrogen Use in Postmenopausal Woman," American Journal of Epidemiology, vol. 107, No. 6, pp. 479-487 (1978). |
Pfeffer, R. I., et al., Coronary Risk and Estrogen Use in Postmenopausal Woman, American Journal of Epidemiology, vol. 107, No. 6, pp. 479 487 (1978). * |
Rosano Giuseppe M. C., et al., "Beneficial effect of estradiol 17-bet on exercise-induced myocardial ischaemia in woman with coronary arter disease. A double blind randomized placebo controlled study" J. Am Coll. Cardiol., vol. 21, No. 2, Suppl. A). pp. 64A, 1993. 42nd Ann. Scientific Session of the Am. Coll. of Cardiology (Mar. 14-18 1993). |
Rosano Giuseppe M. C., et al., Beneficial effect of estradiol 17 bet on exercise induced myocardial ischaemia in woman with coronary arter disease. A double blind randomized placebo controlled study J. Am Coll. Cardiol., vol. 21, No. 2, Suppl. A). pp. 64A, 1993. 42nd Ann. Scientific Session of the Am. Coll. of Cardiology (Mar. 14 18 1993). * |
Rosano, Giuseppe M. C., et al., "Beneficial effect of oestrogen on exercise-induced myocardial ischaemia in woman with coronary artery disease," The Lancet, vol. 342, pp. 133-136 (Jul. 17, 1993). |
Rosano, Giuseppe M. C., et al., Beneficial effect of oestrogen on exercise induced myocardial ischaemia in woman with coronary artery disease, The Lancet, vol. 342, pp. 133 136 (Jul. 17, 1993). * |
Rosenberg, Lynn, et al. "Myocardial Infarction and Estrogen Therapy in Post-Menopausal Women," The New England Journal of Medicine, vol. 294, No. 23, pp. 1256-1259 (1976). |
Rosenberg, Lynn, et al. Myocardial Infarction and Estrogen Therapy in Post Menopausal Women, The New England Journal of Medicine, vol. 294, No. 23, pp. 1256 1259 (1976). * |
Rosenberg, Lynn, et al., "Noncontraceptive Estrogens and Myocardial Infarction in Young Women," JAMA, vol. 244, No. 4, pp. 339-342 (1980). |
Rosenberg, Lynn, et al., Noncontraceptive Estrogens and Myocardial Infarction in Young Women, JAMA, vol. 244, No. 4, pp. 339 342 (1980). * |
Ross, Ronald K., et al. "Menopausal Oestrogen Therapy and Protection from Death from Ischaemic Heart Disease," The Lancet, Apr. 18, 1981, pp. 858-860. |
Ross, Ronald K., et al. Menopausal Oestrogen Therapy and Protection from Death from Ischaemic Heart Disease, The Lancet, Apr. 18, 1981, pp. 858 860. * |
Stampfer, Meir J. et al. "A Prospective Study of Postmenopausal Estrogen Therapy and Coronary Heart Disease," The New England Journal of Medicine, vol. 313, No. 17, pp. 1044-1049 (1985). |
Stampfer, Meir J. et al. A Prospective Study of Postmenopausal Estrogen Therapy and Coronary Heart Disease, The New England Journal of Medicine, vol. 313, No. 17, pp. 1044 1049 (1985). * |
Szklo, Moyses, et al. "Estrogen Use and Myocardial Infarction Risk: A Case-Control Study," Preventive Medicine, vol. 13, pp. 510-516 (1984). |
Szklo, Moyses, et al. Estrogen Use and Myocardial Infarction Risk: A Case Control Study, Preventive Medicine, vol. 13, pp. 510 516 (1984). * |
Wilson, W. F., et al. "Postmenopausal Estrogen Use, Cigarette Smoking, and Cardiovascular Morbidity in Woman Over 50," The New England Journal of Medicine, vol. 313, No. 17, pp. 1038-1043 (1985). |
Wilson, W. F., et al. Postmenopausal Estrogen Use, Cigarette Smoking, and Cardiovascular Morbidity in Woman Over 50, The New England Journal of Medicine, vol. 313, No. 17, pp. 1038 1043 (1985). * |
Cited By (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6319914B1 (en) | 1993-11-05 | 2001-11-20 | Apollo Biopharmaceuticals, Inc. | Cytoprotective effect of polycyclic phenolic compounds |
US20030069217A1 (en) * | 1993-11-05 | 2003-04-10 | Simpkins James W. | Methods of prevention and treatment of ischemic damage |
WO1998022113A1 (en) * | 1996-11-15 | 1998-05-28 | University Of Florida Research Foundation, Incorporated | Methods of prevention and treatment of ischemic damage |
US20040127473A1 (en) * | 1996-12-05 | 2004-07-01 | Reed Michael John | Compound |
US5968918A (en) * | 1997-10-17 | 1999-10-19 | Kanda; Iwao | Method for the prevention of coronary artery spasm |
US6326365B1 (en) | 1999-07-20 | 2001-12-04 | Apollo Biopharmaceutics, Inc. | Methods of prevention and treatment of ischemic damage |
US6339078B1 (en) | 1999-07-20 | 2002-01-15 | University Of Florida Research Foundation, Inc. | Methods of prevention and treatment of ischemic damage |
US20040229856A1 (en) * | 1999-09-21 | 2004-11-18 | Baskaran Chandrasekar | Local delivery of 17-beta estradiol for preventing vascular intimal hyperplasia and for improving vascular endothelium function after vascular injury |
US20070141109A1 (en) * | 1999-09-21 | 2007-06-21 | Baskaran Chadrasekar | Local Deliver of 17-Beta Estradiol for Preventing Vascular Intimal Hyperplasia and for Improving Vascular Endothelium Function after Vascular Injury |
US20040214769A1 (en) * | 2001-01-05 | 2004-10-28 | Claes Ohlsson | Estrogen receptors |
US20060211671A1 (en) * | 2001-01-05 | 2006-09-21 | Claes Ohlsson | Estrogen receptors |
US20050267086A1 (en) * | 2004-05-27 | 2005-12-01 | Migenix Corp. | Compounds and methods for cytoprotection |
US7304171B2 (en) | 2004-05-27 | 2007-12-04 | Migenix Corp. | Compounds and methods for cytoprotection |
US20080171034A1 (en) * | 2004-05-27 | 2008-07-17 | Migenix Corp. | Compounds and methods for cytoprotection |
US20090075888A1 (en) * | 2007-09-13 | 2009-03-19 | University Of North Texas Health Science Center At Fort Worth | Cardiovascular and Brain Cell Therapy Using Intracellular Ryanodine Receptor Modulation by the Estrogen Receptor Beta |
WO2009035929A2 (en) * | 2007-09-13 | 2009-03-19 | University Of North Texas Health Science Center At Fort Worth | Cardiovascular and brain cell therapy using intracellular ryanodine receptor modulation by the estrogen receptor beta |
WO2009035929A3 (en) * | 2007-09-13 | 2009-05-22 | Univ North Texas | Cardiovascular and brain cell therapy using intracellular ryanodine receptor modulation by the estrogen receptor beta |
US20110158947A1 (en) * | 2008-07-11 | 2011-06-30 | Aleksandar Jovanovic | Sulfonylurea receptor and means for treating ischaemia |
Also Published As
Publication number | Publication date |
---|---|
USRE36701E (en) | 2000-05-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
RU2113849C1 (en) | Mixed preparation based on natural estrogens for contraception | |
RU2139056C1 (en) | Hormonal substitutional therapy | |
Liggins et al. | The mechanism of initiation of parturition in the ewe | |
JP3211892B2 (en) | Nitric oxide donor and method for treating anal disease | |
US5512557A (en) | Coronary heart disease treated with 17βoestradiol | |
US6511969B1 (en) | Method for reducing coronary artery reactivity | |
EP1539184B1 (en) | Estrogen replacement regimen | |
Rolland et al. | A new approach to the inhibition of puerperal lactation | |
SI9620058A (en) | Methods and formulations for modulating the human sexual response | |
Brown et al. | Low-dose aspirin: II. Relationship of angiotensin II pressor responses, circulating eicosanoids, and pregnancy outcome | |
Nachtigall | Emerging delivery systems for estrogen replacement: aspects of transdermal and oral delivery | |
KR19980703702A (en) | Pharmaceutical formulation for hormone contraception | |
PL192979B1 (en) | Hormonal preparation consisting of an oestrogen compound and of a progesterone compound | |
Saito et al. | Treatment of overactive bladder with modified intravesical oxybutynin chloride | |
Notelovitz | Effect of natural oestrogens on blood pressure and weight in postmenopausal women | |
Andersen | Excretion of verapamil in human milk | |
McMahon et al. | Guanabenz in essential hypertension | |
CN111012766A (en) | Pharmaceutical composition for preventing and treating pulmonary hypertension and preparation method and application thereof | |
US5968918A (en) | Method for the prevention of coronary artery spasm | |
Fujita et al. | Salt loads attenuate potassium-induced vasodilation of forearm vasculature in humans. | |
USRE35724E (en) | Contraception system and method | |
JP2001513566A (en) | Combination of estrogen with endometrial sparing progestin and endometrial atrophy progestin in oral contraception | |
Åkerlund | Oxytocin antagonists in the treatment of preterm labour | |
US9339458B2 (en) | Use of vaginal insulin sensitizing agents | |
US6602487B1 (en) | Methods and tests for producing and for inhibiting coronary artery vasospasms |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: NATIONAL HEART AND LUNG INSTITUTE, THE, GREAT BRIT Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:COLLINS, PETER;REEL/FRAME:006807/0967 Effective date: 19931021 |
|
STCF | Information on status: patent grant |
Free format text: PATENTED CASE |
|
FEPP | Fee payment procedure |
Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY |
|
CC | Certificate of correction | ||
RF | Reissue application filed |
Effective date: 19980429 |
|
AS | Assignment |
Owner name: STERIX LIMITED, UNITED KINGDOM Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:IMPERIAL COLLEGE OF SCEINCE TECHNOLOGY AND MEDICINE;BATH, UNIVERSITY OF, THE;RESEARCH EXPLOITATION LIMITED;AND OTHERS;REEL/FRAME:010154/0537;SIGNING DATES FROM 19980528 TO 19990528 Owner name: STERIX LIMITED, UNITED KINGDOM Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE;BATH, THE UNIVERSITY OF;RESEARCH EXPLOITATION LIMITED;AND OTHERS;REEL/FRAME:010007/0618 Effective date: 19990528 |
|
FPAY | Fee payment |
Year of fee payment: 4 |
|
FEPP | Fee payment procedure |
Free format text: PAYER NUMBER DE-ASSIGNED (ORIGINAL EVENT CODE: RMPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY |